Objective: To reveal the relationship between ARHL and ferroptosis and screen ferroptosis-related genes (FRGs) in ARHL.Methods: Bioinformatics were used to analyze the hub genes and molecular mechanism of ferroptosis in the aging cochleae. Senescence β-galactosidase staining, iron content detection, and micro malondialdehyde (MDA) assay kits were used to measure β-galactosidase activity, and expression of Fe²⁺ and MDA, respectively. Fluorescence microscope was used for immunofluorescence assay of hub genes. Western blot was used to verify the expression of hub genes in HEI-OC1 cells, cochlear explants, and cochleae of C57BL/6J mice. Data were expressed as mean ± SD of at least three independent experiments.Results: The analysis of bioinformatics confirmed that lactotransferrin (LTF) is the hub gene and CEBPA-miR-130b-LTF network is the molecular mechanism for cochlear ferroptosis. Compared with the control group, the experiments proved that the indicators of ferroptosis, including Fe²⁺, MDA, and LTF were differentially expressed in aging HEI-OC1 cells, aging cochlear explants, and aging cochleae.Conclusion: These results demonstrate that ferroptosis plays an important role in ARHL, and LTF is a potential therapeutic target for ARHL via regulating cochlear ferroptosis.

Background: The stria vascularis (SV), located in the lateral wall of the cochlea, maintains cochlear fluid homeostasis and mechanoelectrical transduction (MET) activity required for sound wave conduction. The pathogenesis of a number of human inheritable deafness syndromes, age related hearing loss, drug-induced ototoxicity and noise-induced hearing loss results from the morphological changes and functional impairments in the development of the SV. In this study, we investigate the implications of intercellular communication within the SV in the pathogenesis of sensorineural hearing loss (SNHL). We aim to identify commonly regulated signaling pathways using publicly available single-cell transcriptomic sequencing (scRNA-seq) datasets. Methods: We analyzed scRNA-seq data, which was derived from studying the cochlear SV in mice with SNHL compared to normal adult mice. After quality control and filtering, we obtained the major cellular components of the mouse cochlear SV and integrated the data. Using Seurat's FindAllMarkers and FindMarkers packages, we searched for novel conservative genes and differential genes. We employed KEGG and GSEA to identify molecular pathways that are commonly altered among different types of SNHL. We utilized pySCENIC to discover new specific regulatory factors in SV subpopulation cells. With the help of CellChat, we identified changes in subpopulation cells showing similar trends across different SNHL types and their alterations in intercellular communication pathways. Results: Through the analysis of the integrated data, we discovered new conserved genes to SV specific cells and identified common downregulated pathways in three types of SNHL. The enriched genes for these pathways showing similar trends are primarily associated with the Electron Transport Chain, related to mitochondrial energy metabolism. Using the CellChat package, we further found that there are shared pathways in the incoming signaling of specific intermediate cells in SNHL, and these pathways have common upstream regulatory transcription factor of Nfe2l2. Combining the results from pySCENIC and CellChat, we predicted the transcription factor Nfe2l2 as an upstream regulatory factor for multiple shared cellular pathways in IC. Additionally, it serves as an upstream factor for several genes within the Electron Transport Chain. Conclusion: Our bioinformatics analysis has revealed that downregulation of the mitochondrial electron transport chain have been observed in various conditions of SNHL. E2f1, Esrrb, Runx1, Yy1, and Gata2 could serve as novel important common TFs regulating the electron transport chain. Adm has emerged as a potential new marker gene for intermediate cells, while Itgb5 and Tesc show promise as potential new marker genes for marginal cells in the SV. These findings offer a new perspective on SV lesions in SNHL and provide additional theoretical evidence for the same drug treatment and prevention of different pathologies of SNHL.

Purpose: The purpose of this study was to analyze the relationship between the degree of high jugular bulb (HJB) and mastoid pneumatization using high-resolution computed tomography (HRCT).Methods: Between April 2019 and June 2022, HRCT of the temporal bone was retrospectively analyzed in 1,025 patients. By excluding the other coexistent pathologies, 113 patients with HJBs were recruited for the study. The degree of the HJBs were defined as follows: Grade I, JB situated between inferior annulus of tympanic membrane and cochlear basal turn (CBT). Grade II, JB situated between CBT and lateral semicircular canal (LSC). Grade III, JB situated above LSC. The volume of mastoid pneumatization was based on HRCT images using a 3D reconstruction.Results: There were 32 male and 81 female subjects (mean age, 41.2 ± 14.0 years; age range, 18–80 years). The male group included 16 Grade I, 28 Grade II and 6 Group III HJB subjects. The female group included 38 Grade I, 62 Grade II and 31 Group III HJB cases. In the different groups of HJB, the mastoid cell volume differences were also not statistically significant (p = 0.165). In the classification, Grade II was most common (90/181, 49.7%).Conclusion: This study found no correlation between mastoid air cell volume and HJB, suggesting that HJB may not affect the mastoid air cell development and disease occurrence. These data must be considered exploratory, requiring more extensive cross-sectional studies.